Dopamine Conjugate Research Articles

Folic acid-based hydrogels co-assembled with protocatechuic acid for enhanced treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) presents a significant therapeutic challenge due to the need for oral drug delivery systems that withstand acidic environment of stomach while effectively targeting intestinal inflammation. To address this issue, we created a novel hydrogel system based on a folic acid (FA)-dopamine (DA) conjugate, co-assembled with protocatechuic acid (PCA), to form F-DP hydrogels. These hydrogels demonstrated robust anti-gastric acid, mucosal adhesive, and injectable properties, enhancing their efficacy for targeted delivery. In DSS-induced colitis mouse models, treatment with F-DP hydrogels resulted in significant therapeutic improvements, including increased body weight, reduced disease activity index (DAI), and maintained colon length. Biochemical assays revealed that F-DP hydrogels significantly enhanced antioxidant enzyme activities (GSH and SOD) and reduced oxidative stress markers (NO and MDA). Histological assessments confirmed effective repair of the colonic mucosal barrier, restoration of tight junction protein ZO-1, and reduction of inflammatory lesions. Furthermore, immunofluorescence staining indicated that F-DP hydrogels facilitated macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby reducing inflammation and promoting tissue repair. Our study demonstrates that F-DP hydrogels show significant potential for improving IBD treatment through enhanced gastric resistance, intestinal adhesion, and synergistic anti-inflammatory effects, warranting further investigation for clinical applications.

Controllable Dopamine Conjugation Boosts Fluorescence, Biocompatibility, and PET Imaging‐Guided Toxicity Assessment of Polycations

AbstractAs well known in bioactives delivery and cancer/inflammation theranostics, polycations have recently extended their biomedical potentials in reducing visceral fat, embolizing body fluid, modulating blood coagulation, and ameliorating hyperammonemia. However, positive charges that dominate various action mechanisms, often raise risks in biosafety concerns. Also, the lack of intrinsic imaging properties of polycations makes it challenging to uncover their pharmacokinetic profiles in living objects. Herein, dopamine conjugation is demonstrated controllable and highly efficient in boosting the fluorescence or even white color emission of various polycations including hyperbranched poly(amido amine) (HPAA), polyethyleneimine and poly‐L‐lysine. By shielding partial surface positive charges, increasing hydrophobicity, and inducing aqueous self‐assembly, dopamine conjugation can significantly enhance the biocompatibility and decrease the toxicity and immunogenicity of polycations. Furthermore, the catechol‐metal binding interaction facilitates the accessibility of polycation‐based positron emission tomography (PET) probes. Different tissue uptake and biodistributions of gallium‐68‐radiolabeled HPAA before and after dopamine conjugation indicate that PET imaging can be a useful supplement to evaluate the dynamic toxicities of polycations.

What Is Wrong with Hyaluronic Acid Chemistry? A 15N/13C Solid-State NMR Re-Evaluation of Its Dopamine Conjugates

In this work, a systematic 15N/13C solid-state NMR investigation is performed on three dopamine (DA) conjugates of hyaluronic acid, considered in both its native (HA) and NaIO4-oxidized (HAOx) forms. Two of them, here named HAEDC-DA and HAOx-DA, have been previously introduced as covalent conjugates involving DA amine nitrogen: the former by EDC-mediated amide bond formation, and the latter by reaction of the Schiff base with the aldehyde moieties presumed to exist in HAOx. The third conjugate, HA-DA, is reported here for the first time; it is obtained by simply mixing hyaluronan with DA∙HCl at pH 5. The 15N ss-NMR spectra were found to be consistent in all the systems, and the DA molecules were found to be in their charged -NH3+ form, which contradicts the HAEDC-DA/HAOx-DA covalent bonding schemes proposed in the literature. The 13C ss-NMR results add useful new insights into the structure and interaction patterns of the conjugates. All of our findings are relevant for future practical applications, for instance in developing novel HA-based hydrogels. In addition, the present study demonstrates the importance of using the most appropriate analytical tools when investigating composite systems due to the complexity of hyaluronic acid conjugates. Solid-state NMR proved essential to answering the question in the title: actually, there is nothing wrong with hyaluronic acid chemistry; the claimed covalent bonds between DA and the HA(HAOx) chain do not exist in these systems, because the conditions for their formation do not hold in practice.

Neurotransmitter ligand effect of dopamine and cortisol conjuation on ZnO nanoparticles embedded polyvinylphenol resistive switching device

In this paper, dopamine (DA) and cortisol (CORT), two kinds of neurotransmitters, were adopted as a ligand or surface modification agent on zinc oxide (ZnO) nanoparticles (NPs) to modulate resistive switching (RS) property of the ZnO NPs embedded into polyvinylphenol (PVP) hybrid matrix. Here, digital and analog RS behaviors were demonstrated with the DA and CORT conjugations showing different ligand influence on the RS properties, respectively. For the hybrid layer, operations of bistable ON/OFF and multileveled resistance or conductance could coexist depending on the thickness and concentration of the ZnO NPs. First, conjugation of the DA on the ZnO NPs could reveal distinct memristive behaviors, which demonstrated potentiation of analog RS mode by showing gradually increased windows of the I–V hysteresis by consecutive sweeps, which were distinguished from the unconjugated ZnO NPs embedded PVP device. Secondly, in the other hand, conjugation of the CORT as the ZnO NPs’ ligand could demonstrate enhanced depression characteristics unlike the potentiation behavior induced by the DA conjugation. Therefore, since the biological neurotransmitters of DA and CORT were found to influence the RS behaviors, a novel development of bioelectronic neuromorphic device implemented for a direct interface between biological neuro-system and electronic RS device can be envisioned through this study.

A hypothesis on the equilibrium between dopamine toxicity and detoxification: The roles of NQO2 and UDP-glucuronosyltransferases

NQO2 and tyrosine hydroxylase are co-expressed in dopaminergic neurons. These neurons produce dopamine, a diol, which, under aerobic conditions, can spontaneously revert to the more stable form, the o-quinone. O-quinones are preferred substrates of NQO2 over p-quinones. In ad hoc conditions, NQO2 reduces o-quinones into the original diols, leading to a futile cycle, the endpoint of which is a strong local production of reactive oxygen species that is deadly for the cells. This futile cycle can be interrupted by the conjugation of dopamine with UDP-glucuronic acid, leading to a glucuronide that cannot be part of the cycle because the glucuronide is not a substrate of NQO2. In this paper, we confer whether this futile cycle could be one of the causes of the specific death of dopaminergic neuronal population that is the signature of some degenerative diseases.

Fluorescent Magnetic Nanoparticles for Bioimaging through Biomimetic Surface Modification

Nanostructured materials and systems find various applications in biomedical fields. Hybrid organo-inorganic nanomaterials are intensively studied in a wide range of areas, from visualization to drug delivery or tissue engineering. One of the recent trends in material science is biomimetic approaches toward the synthesis or modification of functional nanosystems. Here, we describe an approach toward multifunctional nanomaterials through the biomimetic polymerization of dopamine derivatives. Magnetite nanoparticles were modified with a combination of dopamine conjugates to give multifunctional magneto-fluorescent nanocomposites in one synthetic step. The obtained material showed excellent biocompatibility at concentrations up to 200 μg/mL and an in vivo biodistribution profile typical for nanosized formulations. The synthesized systems were conjugated with antibodies against HER2 to improve their selectivity toward HER2-positive cancer cells. The produced material can be used for dual magneto-optical in vivo studies or targeted drug delivery. The applied synthetic strategy can be used for the creation of various multifunctional hybrid nanomaterials in mild conditions.

Oxidized Alginate Dopamine Conjugate: A Study to Gain Insight into Cell/Particle Interactions.

Background: We had previously synthetized a macromolecular prodrug consisting of oxidized Alginate and dopamine (AlgOx-Da) for a potential application in Parkinson disease (PD). Methods: In the present work, we aimed at gaining an insight into the interactions occurring between AlgOx-Da and SH-SY5Y neuronal cell lines in view of further studies oriented towards PD treatment. With the scope of ascertaining changes in the external and internal structure of the cells, multiple methodologies were adopted. Firstly, fluorescently labeled AlgOx-Da conjugate was synthetized in the presence of fluorescein 5(6)-isothiocyanate (FITC), providing FITC-AlgOx-Da, which did not alter SH-SY5Y cell viability according to the sulforhodamine B test. Furthermore, the uptake of FITC-AlgOx-Da by the SH-SY5Y cells was studied using scanning near-field optical microscopy and assessments of cell morphology over time were carried out using atomic force microscopy. Results: Notably, the AFM methodology confirmed that no relevant damage occurred to the neuronal cells. Regarding the effects of DA on the intracellular reactive oxygen species (ROS) production, AlgOx-Da reduced them in comparison to free DA, while AlgOx did almost not influence ROS production. Conclusions: these findings seem promising for designing in vivo studies aiming at administering Oxidized Alginate Dopamine Conjugate for PD treatment.

Bio-Inspired Surface Modification of Magnetite Nanoparticles with Dopamine Conjugates.

Organically-coated nanomaterials are intensively studied and find numerous applications in a wide range of areas from optics to biomedicine. One of the recent trends in material science is the application of bio-mimetic polydopamine coatings that can be produced on a variety of substrates in a cost-efficient way under mild conditions. Such coatings not only modify the biocompatibility of the material but also add functional amino groups to the surface that can be further modified by classic conjugation techniques. Here we show an alternative strategy for substrates modification using dopamine conjugates instead of native dopamine. Compared to the classic scheme, the proposed strategy allows separation of the “organic” and “colloidal” stages, and simplified identification and purification steps. Modification with pre-modified dopamine made it possible to achieve high loading capacities with active components up to 10.5% wt. A series of organo-inorganic hybrids were synthesized and their bioactivity was analyzed.

Assessment of dopamine-conjugated decellularized bovine tendon extracellular matrix as a bioadhesive

In this study, a bioadhesive based on catechol and extracellular matrix was developed and characterized in detail. At first, cells were removed from bovine tendon tissue to obtain tendon extracellular matrix (t-ECM), then its acellularity was confirmed. The decellularized tissue was digested enzymatically to yield an injectable form of t-ECM with a high content of protein, collagen and sulfated glycosaminoglycans. Next, conjugation of dopamine to t-ECM was performed under acidic, neutral, and basic pH conditions, either in the presence of O2 or under N2 flow. Conjugation of dopamine to t-ECM was determined by FT-IR, 1H NMR and UV–vis analysis, while catechol groups in the structures were quantified by Arnow method. The findings revealed that neutral and basic conditions are more suitable for dopamine conjugation. The physical properties of the bioadhesive were also determined by swelling and mass loss analysis. The conjugates exhibited good cytocompatibility and hemocompatibility and showed good cell adhesion. The lap-shear test using skin tissue showed that the t-ECM-dopamine conjugate has high adhesive strength and can be considered as a potential bioadhesive for the future.

Mussel-Inspired Catechol Functionalisation as a Strategy to Enhance Biomaterial Adhesion: A Systematic Review.

Biomaterials have long been explored in regenerative medicine strategies for the repair or replacement of damaged organs and tissues, due to their biocompatibility, versatile physicochemical properties and tuneable mechanical cues capable of matching those of native tissues. However, poor adhesion under wet conditions (such as those found in tissues) has thus far limited their wider application. Indeed, despite its favourable physicochemical properties, facile gelation and biocompatibility, gellan gum (GG)-based hydrogels lack the tissue adhesiveness required for effective clinical use. Aiming at assessing whether substitution of GG by dopamine (DA) could be a suitable approach to overcome this problem, database searches were conducted on PubMed® and Embase® up to 2 March 2021, for studies using biomaterials covalently modified with a catechol-containing substituent conferring improved adhesion properties. In this regard, a total of 47 reports (out of 700 manuscripts, ~6.7%) were found to comply with the search/selection criteria, the majority of which (34/47, ~72%) were describing the modification of natural polymers, such as chitosan (11/47, ~23%) and hyaluronic acid (6/47, ~13%); conjugation of dopamine (as catechol “donor”) via carbodiimide coupling chemistry was also predominant. Importantly, modification with DA did not impact the biocompatibility and mechanical properties of the biomaterials and resulting hydrogels. Overall, there is ample evidence in the literature that the bioinspired substitution of polymers of natural and synthetic origin by DA or other catechol moieties greatly improves adhesion to biological tissues (and other inorganic surfaces).

Development of the mussel-inspired pH-responsive hydrogel based on Bletilla striata polysaccharide with enhanced adhesiveness and antioxidant properties

Recently, smart hydrogels have attracted much attention for their abilities to respond to subtle changes in external and internal stimuli. Also, natural polysaccharide-based biomaterials are more appealing for their biocompatibility and biodegradability. However, limitations owing to their complex compositions and mechanisms, cumbersome synthetic routes, and single function call for a simple and effective strategy to develop novel multifunctional smart hydrogels. Herein, this developed work was achieved based on Bletilla striata polysaccharide (BSP), a kind of natural glucomannan with diverse bioactivities and biocompatibility, we fabricated a low-cost multifunctional hydrogel by oxidizing the catechol groups of carboxymethylated BSP(CBSP)-dopamine(DA) conjugate with adhesion, antioxidant, and pH-responsive properties. In this hydrogel system, CBSP as the backbone material, was negatively charged and conferred the hydrogel with pH sensitivity. The presence of catechol groups greatly enhanced the tissue adhesion and antioxidant capacities of the hydrogel. Meanwhile, the highly porous structure of hydrogel allowed berberine to be encapsulated and released to exhibit excellent and long-lasting antibacterial activity. In summary, the adhesion, antioxidant, pH-sensitive, and antibacterial multifunctional hydrogel showed massive potential in the biomedical field.

Development of alginate and gelatin-based pleural and tracheal sealants

Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. Statement of significancePneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application.

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration.

Nose-to-brain delivery: A comparative study between carboxymethyl chitosan based conjugates of dopamine

Herein, the synthesis of a novel polymeric conjugate N,O-CMCS-Dopamine (DA) based on an amide linkage is reported. The performances of this conjugate were compared with those of an analogous N,O-CMCS-DA ester conjugate previously studied (Cassano et al., 2020) to gain insight into their potential utility for Parkinson's disease treatment. The new amide conjugate was synthesized by standard carbodiimide coupling procedure and characterized by FT-IR, 1H NMR spectroscopies and thermal analysis (Differential Scanning Calorimetry). In vitro mucoadhesive studies in simulated nasal fluid (SNF) evidenced high adhesive effect of both ester and amide conjugates. Results demonstrated that the amide conjugate exerted an important role to prevent DA spontaneous autoxidation both under stressed conditions and physiological mimicking ones. MTT test indicated cytocompatibility of the amide conjugate with Olfactory Ensheating Cells (OECs), which were shown by cytofluorimetry to internalize efficiently the conjugate. Overall, among the two conjugates herein studied, the N,O-CMCS-DA amide conjugate seems a promising candidate for improving the delivery of DA by nose-to-brain administration.

Molecular Modeling Analysis of Chitosan-Dopamine Blend with Iron Oxide Nanoparticles for Tissue Engineering Applications

This study aims to mimic mussel adhesive protein (MAPs) by mussel-inspired metal-coordination chemistry at the polymer−particle interface using iron oxide nanoparticles (Fe3O4 NPs) and catechol−polymer as the building blocks. Catechol group of dopamine conjugates with chitosan backbone and provides additional adhesion strength with tissue surfaces. Molecular modeling, including two different methods, Quantitative structure-activity relationship (QSAR) and molecular electrostatic potential (MESP), was used to study the suggested tissue adhesive's physical and structural properties. Four positions of Fe3O4 NPs to connect with chitosan-dopamine blend were proposed. The third site was preferred by following the bandgap energy (ΔE) results and the total dipole moment (TDM).

Mussel-inspired poly(γ-glutamic acid)/nanosilicate composite hydrogels with enhanced mechanical properties, tissue adhesive properties, and skin tissue regeneration

It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H2O2, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. Statement of significanceRecently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.

Enzymatically Cross-Linked Poly(γ-glutamic acid) Hydrogel with Enhanced Tissue Adhesive Property.

Enzymatic cross-linking of polymer-catechol conjugates in the presence of horseradish peroxidase (HRP) and H2O2 has emerged as an important method to fabricate in situ-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, because of the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of the polymer with optimized tissue adhesive property is still challenging. In this study, a poly(γ-glutamic acid) (γ-PGA)-dopamine (PGADA) conjugate was synthesized, and in situ hydrogels were fabricated via enzymatic cross-linking of a catechol moiety. To optimize the tissue adhesive property of the PGADA hydrogel, the effect of various factors, such as polymer concentration, catechol substitution degree (DS), HRP concentration, and H2O2 content, on the gelation behavior and mechanical strength was investigated. The gelation behavior of PGADA hydrogels was characterized using a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength in vitro and ex vivo.

Dual-Response Detection of Oxidized Glutathione, Ascorbic Acid, and Cell Imaging Based on pH/Redox Dual-Sensitive Fluorescent Carbon Dots.

The pH/redox dual-sensitive fluorescent carbon dots (pHRCDs) with the fluorescence quantum yield of 16.97% were synthesized by the pyrolysis of l-glutamic acid (l-glu) and dopamine (DA). Compared with the quantum dot (QD)–dopamine conjugate, when the pH value of the solution was changed from neutral to alkaline, the pHRCDs exhibited unique optical phenomenon including red-shift of fluorescence peak and the fluorescence intensity first decreasing from pH 7 to 10 and then increasing from pH 10 to 13. The pHRCDs could be developed for a discriminative and highly sensitive dual-response fluorescent probe for the detection of oxidized glutathione (GSSG) and ascorbic acid (AA) activity in human blood. Under the optimized experimental conditions, the dual-response fluorescent probe can detect GSSG and AA in the linear range of 1.2–3.6 and 27–35 μM with the detection limits of 0.1 and 3.1 μM, respectively. In addition, the pHRCDs demonstrated low cytotoxicity and good biocompatibility, which can be well applied to in vitro cell imaging, and the pHRCDs/GSH fluorescence system has been successfully developed for the detection of AA in real samples.

Enzymatically Crosslinked Poly(γ -Glutamic Acid) Hydrogel with Enhanced Tissue Adhesive Property

Enzymatic crosslinking of polymer-catechol conjugate in the presence of horseradish peroxidase (HRP) and H2O2 has emerged as an important method to fabricate in situ-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, due to the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of polymer with optimized tissue adhesive property is still challenging. In this study, poly(γ-glutamic acid) (γ-PGA)-dopamine conjugate (PGADA) was synthesized, and in situ hydrogels were fabricated via enzymatic crosslinking of catechol moiety. To optimize the tissue adhesive property of the PGADA hydrogel, the effect of various factors, such as polymer concentration, catechol substitution degree (DS), HRP concentration and H2O2 content, on the gelation behavior and mechanical strength was investigated. The gelation behavior of PGADA hydrogels was characterized by a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength in vitro and in vivo.

Dopamine-conjugated apoferritin protein nanocage for the dual-targeting delivery of epirubicin

Objective(s): Nanocarriers are drug delivery vehicles, which have attracted the attention of researchers in recent years, particularly in cancer treatment. The encapsulation of anticancer drugs using protein nanocages is considered to be an optimal approach to reducing drug side-effects and increasing the bioavailability of anticancer drugs. Epirubicin (EPR) is an active chemotherapeutic medication used in the treatment of breast cancer. However, the toxicity of this drug against normal cells is a considerable limitation in therapy. EPR toxicity could be reduced using nanocarriers and dual-targeted drug delivery. Dual-targeted drug delivery system was developed by the conjugation of dopamine (DA) with horse spleen apoferritin (HsAFr)-encapsulated EPR to overcome the limitations of chemotherapeutic EPR in breast cancer treatment. HsAFr-EPR-DA complexes could target the scavenger receptors, transferrin receptors 1, and DA receptors, which are overexpressed on breast cancer cells. Materials and Methods: UV-Visible, fluorescence, and circular dichroism (CD) spectroscopic techniques and transmission electronic microscope (TEM) have been applied to characterize HsAFr-EPR-DA complexes. In the present study, we utilized human breast cancer cell line (MCF-7), aiming to compare the cytotoxicity of HsAFr-EPR-DA complexes to free EPR. Results: The toxicity was measured using the MTT assay, which demonstrated that the dual-targeted nanocarrier (HsAFr-EPR-DA) enhanced cytotoxicity against MCF-7 more significantly compared to non-targeted nanocarriers.Conclusion: The findings of the current research indicated that the synthesized HsAFr-DA complex was an optimal nanocarrier for the dual-targeted delivery of anticancer drugs.